ACTION AND MECHANISM

- [MUCOLYTIC]. It is the N-acetylated derivative of the natural amino acid cysteine. It reduces the viscosity of bronchial secretions, promoting their elimination, probably due to the presence of a free thiol group. This group is capable of breaking the disulfide bonds that maintain the three-dimensional structure of mucoproteins, resulting in the fluidification of the secretion. Its effects are pH-dependent, being maximum at pH between 7 and 9.

PATIENT ADVICE

- It is recommended to drink plenty of water during treatment.

- The preparation may have a slight sulphurous odour, which is characteristic of the active ingredient and not an alteration of the preparation.

- You should notify your doctor if you experience generalized itching throughout your body.

- If symptoms persist or worsen after five days, it is advisable to consult a doctor.

CONTRAINDICATIONS

- Hypersensitivity to acetylcysteine or any other component of the medication.

ADVANCED AGE

No specific problems have been described in this age group.

EFFECTS ON DRIVING

Acetylcysteine does not usually cause drowsiness, but some cases have been reported in rare cases. Caution is recommended when driving until it is relatively certain that the treatment does not adversely affect the patient's ability.

PREGNANCY

Animal Safety: Animal studies have not shown direct or indirect effects indicative of reproductive toxicity.

Safety in humans: Adequate and well-controlled studies have not been conducted in humans, so the use of this medication is only acceptable in the absence of safer therapeutic alternatives.

Effects on fertility: No specific studies have been conducted in humans.

PHARMACOKINETICS

- Absorption: Following oral administration of a 200-600 mg dose, it is rapidly absorbed, reaching a Cmax of 0.35-4 mcg/ml after 0.5-1 hour. Its bioavailability is very low (4-10%), probably due to intense intestinal and first-pass hepatic metabolism.

- Distribution: It circulates in plasma both freely and bound to proteins (50%) by labile disulfide bridges or covalent peptide bonds. It diffuses extensively into extracellular fluids, primarily located in bronchial secretions. Its total concentration is 0.33–0.47 l/kg.

- Metabolism: It undergoes intense intestinal and hepatic metabolism, giving rise to sulfur derivatives such as cysteine, N-acetylcystine, N,N-acetylcystine or glutathione.

- Elimination: Acetylcysteine is eliminated by metabolism (70%) and subsequent excretion in urine, either in free form (30%) or as metabolites. Its elimination half-life is 6.25 hours (oral) or 5.58 hours (intravenous).

Pharmacokinetics in special situations:

- Children: After intravenous administration, elimination half-life values of 11 hours have been found.

- Hepatic impairment: The elimination half-life is increased by 80% in patients with severe hepatic impairment or with primary or secondary biliary cirrhosis.

INDICATIONS

- [BRONCHIAL HYPERVISCOSITY].

INTERACTIONS

- Antibiotics. Acetylcysteine may be incompatible with amphotericin B, sodium ampicillin, cephalosporins, erythromycin lactobionate, or some tetracyclines. It is recommended to separate doses by at least two hours.

- Antitussives. Acetylcysteine increases the fluidity of bronchial secretions, so it is not recommended to administer it with antitussives, which could inhibit the cough reflex and lead to pulmonary obstruction.

- Drugs that inhibit bronchial secretion (anticholinergics, tricyclic antidepressants, H1 antihistamines, antiparkinsonian agents, MAOIs, neuroleptics). They may antagonize the effects of acetylcysteine.

- Nitroglycerin. Acetylcysteine may enhance the vasodilatory effects of nitroglycerin and its adverse reactions at very high doses (100 mg/kg).

- Metal salts. Acetylcysteine may have certain chelating effects on some metals such as gold, calcium, or iron, thereby decreasing their absorption. It is recommended to separate the intake of mineral supplements from acetylcysteine by at least two hours.

LACTATION

Animal safety: no data available.

Human safety: It is unknown whether acetylcysteine is excreted in breast milk. A risk to nursing infants cannot be excluded. A decision should be made whether to discontinue breastfeeding or to discontinue/discontinue therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman.

CHILDREN

Acetylcysteine can be used in children, although a dosage form appropriate for these patients should be selected. Consult the dosage form.

RULES FOR CORRECT ADMINISTRATION

Administration with food : It is recommended to take acetylcysteine with food. If administered as a single dose, it is advisable to do so in the morning.

POSOLOGY

- Adults, oral: 5 ml (200 mg)/8 h, with food, or 15 ml (600 mg)/24 h in a single dose, preferably in the morning.
- Children and adolescents under 18 years of age, oral: safety and efficacy have not been evaluated.
Missed dose: Take as soon as possible if the missed dose has been missed. Otherwise, skip the missed dose. Do not double the dose at the next missed dose.
Duration of treatment: If symptoms do not improve or worsen after 5 days of treatment, or if they are accompanied by fever, rash, headache, or persistent sore throat, consult your doctor and/or pharmacist.

PRECAUTIONS

- [LIVER FAILURE] severe, [LIVER CIRRHOSIS]. In these patients, clearance may be decreased, with a consequent increased risk of adverse reactions, so close monitoring of the patient is recommended due to the risk of anaphylactic adverse reactions.- [PEPTIC ULCER]. Acetylcysteine may occasionally cause nausea and vomiting, especially at high doses, thus increasing the risk of gastric bleeding. Furthermore, it has also been postulated that acetylcysteine ​​may increase the fluidity of gastric mucus, leading to a decrease in its protective action. Extreme caution is recommended in patients with peptic ulcer.- [ASTHMA]. In patients with asthma, severe [RESPIRATORY FAILURE] or diseases that present with [BRONCHIAL SPASM], an increase in the fluidity of secretions may lead to airway obstruction if expectoration is inadequate. Therefore, extreme caution is recommended. - Increased expectoration. At the beginning of treatment, an increase in expectoration may occur due to the increased fluidity of secretions. This effect decreases after several days of treatment. If symptoms persist or worsen after five days of treatment, it is advisable to re-evaluate the clinical situation.

PRECAUTIONS RELATED TO EXCIPIENTS

- This medicine contains sodium salts, which should be taken into account in patients on a low-sodium diet.

ADVERSE REACTIONS

Adverse reactions to acetylcysteine are rare, mild, and transient. The most common adverse reactions are:

- Digestive. [NAUSEA], [VOMITING], [DIARRHEA] and [GASTRIC HYPERACIDITY] may occasionally occur, especially when used at high doses.

- Liver. Some cases of [elevated transaminases] have been reported following the administration of large doses of acetylcysteine, which reversed within a few days of discontinuing treatment.

- Neurological/psychological. Some cases of [HEADACHE], [DROWSINESS] have been reported.

- Respiratory. These are usually exclusive to administration by inhalation. [RHINORRHEA], [BRONCHITIS], [TRACHEITIS], [HEMOPTYSIS] and [BRONCHIAL SPASM] may occur.

- Eyepieces. [BLURRED VISION].

- Ear and labyrinth disorders: [TINNITUS].

- Allergic/dermatological. [HYPERSENSITIVITY REACTIONS] may occur 30-60 minutes after administration, presenting with generalized [URTICARIA], moderate [FEVER], [SKIN RASHES], [PRURITUS], [ANGIOEDEMA], [DYSPNEA], and [HYPOTENSION]. These reactions are more frequent and severe when administered parenterally and can be fatal, whereas they are rare when administered orally or by inhalation.

In the event of allergic reactions, it is recommended to temporarily discontinue treatment and administer H1-antihistamines and, if necessary, adrenaline. If the allergic reaction recurs, treatment should be discontinued and not restarted.

- General. [HYPERHIDROSIS].

ADVERSE REACTIONS RELATED TO EXCIPIENTS

- Because it contains methyl parahydroxybenzoate, it may cause [PARABEN ALLERGY], possibly delayed.

OVERDOSE

Symptoms: Acetylcysteine has been administered to humans at doses of up to 500 mg/kg/24 hours without causing side effects, so the possibility of poisoning due to overdose of this active ingredient can be ruled out. However, in the case of massive ingestion, an intensification of adverse effects, primarily gastrointestinal, is expected. Treatment: Symptomatic treatment should be used. The airways should be kept free of secretions, with the patient lying down and bronchial suction performed. If deemed necessary, and within 30 minutes of ingestion, gastric lavage should be performed.